Increased activity of Pgp multidrug transporter in patients with Helicobacter pylori infection

AIM: To determine whether local antibiotic resistance involves P-glycoprotein (Pgp)-mediated active drug out-pumping during Helicobacter pylori (H pylori) infection treatment with classic antibiotic therapy. METHODS: Pgp activity was determined in gastric mucosa biopsy specimens obtained from 53 patients with pathohistologically verified gastritis and microbiologically confirmed H pylori infection, and compared with the Pgp activity in 12 control subjects with normal endoscopic findings. The H pylori positive patients were treated with short-term 7-d therapy consisting of two antibiotics (amoxicillin and azithromycin/metronidazole and clarithromycin) and a proton pump inhibitor. Pgp activity was determined by flow cytometry in the test of rhodamine dye efflux and quantified as mean fluorescence ratio (RMF). RESULTS: Upon the first cycle, H pylori was successfully eradicated in 20 patients, whereas therapy was continued in 33 patients. In the course of antibiotic therapy, RMF increased (P＜0.05) and gastric cells showed higher rhodamine dye efflux. The mean pre-treatment RMF values were also higher (P＜0.0001) in patients with multiple therapeutic failure than in those with successful H pylori eradication and control subjects. CONCLUSION: Pgp might be one of the causes of therapy failure in patients with H pylori and antibiotic therapy could be chosen and followed up on the basis of the Pgp transporter local activity.     

Comment on “A meta-analysis of fracture risk and bone mineral density in patients with systemic sclerosis”

Clinical Rheumatology -     

Hypermagnesemia disturbances in rats,NO-related: pentadecapeptide BPC 157 abrogates, <Emphasis Type="SmallCaps">l</Emphasis>-NAME and <Emphasis Type="SmallCaps">l</Emphasis>-arginine worsen

Aim

Stable gastric pentadecapeptide BPC 157, administered before a high-dose magnesium injection in rats, might be a useful peptide therapy against magnesium toxicity and the magnesium-induced effect on cell depolarization. Moreover, this might be an NO-system-related effect. Previously, BPC 157 counteracts paralysis, arrhythmias and hyperkalaemia, extreme muscle weakness; parasympathetic and neuromuscular blockade; injured muscle healing and interacts with the NOS-blocker and NOS-substrate effects.

Main methods

Assessment included magnesium sulfate (560 mg/kg intraperitoneally)-induced muscle weakness, muscle and brain lesions, hypermagnesemia, hyperkalaemia, increased serum enzyme values assessed in rats during and at the end of a 30-min period and medication (given intraperitoneally/kg at 15 min before magnesium) [BPC 157 (10 µg, 10 ng), l-NAME (5 mg), l-arginine (100 mg), alone and/or together]. In HEK293 cells, the increasing magnesium concentration from 1 to 5 mM could depolarize the cells at 1.75 ± 0.44 mV.

Key findings

l-NAME + magnesium-rats and l-arginine + magnesium-rats exhibited worsened severe muscle weakness and lesions, brain lesions, hypermagnesemia and serum enzymes values, with emerging hyperkalaemia. However, l-NAME + l-arginine + magnesium-rats exhibited all control values and normokalaemia. BPC 157 abrogated hypermagnesemia and counteracted all of the magnesium-induced disturbances (including those aggravated by l-NAME or l-arginine). Thus, cell depolarization due to increasing magnesium concentration was inhibited in the presence of BPC 157 (1 µM) in vitro.

Significance

BPC 157 likely counteracts the initial event leading to hypermagnesemia and the life-threatening actions after a magnesium overdose. In contrast, a worsened clinical course, higher hypermagnesemia, and emerging hyperkalaemia might cause both l-NAME and l-arginine to affect the same events adversely. These events were also opposed by BPC 157.

     

DNA methylation and breast cancer-associated variants

Breast Cancer Research and Treatment - A breast cancer polygenic risk score (PRS) comprising 313 common variants reliably predicts disease risk. We examined possible relationships between genetic...     

Is there higher percentage of undetected osteopenia and osteoporosis among patients with ulcerative colitis in Saudi Arabia?

Detection of prevalence and development of osteopenia or osteoporosis in patients with inflammatory bowel disease using only bone mineral density could be inappropriate to detect all individuals at risk for osteoporosis. Numerous patients could remain undetected by using only bone mineral density as a screening method, especially in patients with ulcerative colitis. Therefore, trabecular bone score should be used as a complementary method.     

Wartime open globe eye injuries

Background  

Open globe injuries are the most serious eye injuries in war as in peace time. The purpose of this study is to analyze wartime open globe eye injuries in 72 patients treated at the Department of Ophthalmology, Clinical Hospital of Split from July 1991 to April 1993, during the intensive war in Croatia and Bosnia and Herzegovina, and to evaluate crucial factors responsible for the functional success of the treatment.     

Translating microRNAs into biomarkers: What is new for pediatric cancer?

Since their discovery in 2008, cell-free circulating microRNAs have been considered potential biomarkers for various conditions, including pediatric cancer. Diagnosis of pediatric cancer still relies on clinical signs, which sometimes may be non-specific or appear at later stages. Thus, there is a need for a better understanding of molecules that allow a less invasive, early and effective method of cancer diagnosis. Despite the efforts of many researches to set specific miRNAs to be routinely used as diagnostic molecules, no miR has been currently utilized so far. In this study, we review the recent discoveries on circulating miRNAs in blood of patients suffering from the following pediatric cancers: osteosarcoma, rhabdomyosarcoma, Wilms tumor, acute myeloid leukemia, acute lymphocytic leukemia, retinoblastoma and neuroblastoma. We also focus on the roles of circulating miRs in tumorigenesis pathways, the methodological approaches used to detect and quantify circulating miRs, and discuss the challenges in using them routinely as biomarkers for pediatric cancers.     

Determination of hydrazine in a meningococcal C conjugate vaccine intermediary product

In Brazil, polysaccharide–protein conjugate vaccine against Neisseria meningitidis group C (MenCPS-TT) using hydrazine-activated-tetanus toxoid (TT) as a carrier protein has been developed. Because of the toxicity of hydrazine in humans, it is necessary to monitor this substance's process control step during the vaccine production. The electroanalytical methodology was developed and validated for the determination of hydrazine during the process control of MenCPS-TT vaccine production by differential pulse polarography. The reduction potential was −0.95 V in acetone and sulphuric acid solution. The method presented linear range between 30 and 150 μg L⁻¹and recovery of 93.5 ± 0.8%.     

Hand dominance during constant force isometric contractions: evidence of different cortical drive commands

The purpose of this study was to investigate force variability and sensoriomotor strategies of dominant and nondominant hands of right and left-handed subjects during a submaximal isometric force production task. Twelve right-handed adults (9 men and 3 women; 23?±?3?year) and twelve left-handed adults (4 men and 8 women; 24?±?3?year) performed an isometric constant force contraction sustained at 30 and 50% of maximal force for 10?s. Surface EMG signals were obtained from forearm flexors and extensors. Force signals were analyzed in the time (CV of force) and frequency (0-10?Hz) domain. The neural activation of the involved muscles was investigated from the EMG structure using the cross-wavelet spectra of the interference EMG signals of six different frequency bands of the EMG signals were quantified (5-13, 13-30, 30-60, 60-100, 100-150 and 150-200?Hz). The major findings were: (1) dominant and nondominant hands of right- and left-handed subjects exhibited similar CV of force; (2) the power spectrum of force is influenced by handedness, with greater 1-3?Hz oscillations for left-handed subjects when compared to right-handed subjects; (3) right-handed subjects have greater 30-60?Hz neuromuscular activation when compared to left-handed subjects. Our results indicate that right-handed individuals may rely preferentially in visual feedback to carry out a task with visual and proprioceptive feedback because of the left hemisphere specialization on the visuomotor control.